Peptide derivatives of phosphonic and phosphinic acids containing all amino acids other than glycine in the L-configuration are disclosed in U.S. Pat. No. 4,016,148 issued Apr. 5, 1977. These compounds are disclosed to be useful as potentiators of antibiotics including D-cycloserine.
British Pat. No. 1,356,723 describes an antibiotic SF-1293 which is a peptide phosphinic acid. However, this substance is distinguishable from the present compounds in that the phosphinic acid moiety is at the amino terminus in the prior art structure while it is at the carboxy terminus in the instant compounds. Additionally, while no indication is given in this patent as to the configuration of the amino acids, since the substance is produced by fermentation it is no doubt comprised exclusively of the natural or L-amino acids. Finally, the prior art compound is indicated to be an antibiotic primarily an anti-fungal agent with no indication of any potentiating effectiveness for other antibiotics.
A paper by Haricharan et al., J. Org. Chem. 40, 470 (1975) discloses the synthesis of dipeptides of aminophosphonic acids. The amino terminal amino acid in each instance is glycine which are compounds specifically excluded from the scope of the present invention due to the fact that R.sup.3 in the instant compounds is other than hydrogen (R.sup.3 =hydrogen would provide glycine) and further by the requirement that the amino terminal amino acid have the D configuration.
The presence of 2-aminoethylphosphonic acid from hydrolyzates of fractions derived from marine invertebrates was reported by Quin, Biochemistry 4 (2), 324 (1965). It was indicated that this compound was present in protein materials but the amino group apparently was blocked and the structure of the peptide was indeterminate.
Phosphonopeptides have also been disclosed in prior copending applications as follows: Ser. No. 707,158, filed July 21, 1976; Ser. No. 793,326, filed May 3, 1977 and Ser. No. 793,327, filed May 3, 1977.